The Value Of Neprilysin In Cardiac Insufficiency With Preserved Ejection Fraction-A Pilot Study

Background and Objective:The incidence and mortality of heart failure(HF)are high,and the proportion of HFpEF patients in total heart failure varies from 22% to 73%.Numerous rognostic markers of death and/or HF hospitalization have been identified in patients with HF.However,their clinical applicability is limited and precise risk stratification in HF remains challenging.In PARADIGM-HF trial,in death from cardiovascular causes and the primary endpoint(cardiovascular death or hospitalization secondary to HF),patients with LCZ696(ARNi)compared to enalapril has fallen sharply.Neprilysin(NEP)becomes a target for the treatment of heart failure。Studies have shown that neprilysin is a biomarker for the diagnosis and prognosis of HFrEF and ADH.These are our purposes,to study the level of NEP in patients of cardiac insufficiency with preserved ejection fraction,the relationship between NEP and NT-pro BNP,and to explore the application value of NEP in cardiac insufficiency with preserved ejection fraction.Methods:A total of 269 consecutive patients admitted in the cardiovascular ward of the Second Affiliated Hospital of Nanchang University 02.01.2016 to 02.20.2017.There are including 121 patients as symptomatic cardiac insufficiency with preserved ejection fraction(HFpEF),96 patients as asymptomatic cardiac insufficiency with preserved ejection fraction and 52 patients without cardiac insufficiency as control group.Serum NEP level was tested by enzyme-linked immunosorbent assay(ELISA).At the same time,the general clinical data of the patient were collected: age,gender,heart rate,blood pressure,past history,medication history,biochemical indicators,color ultrasound indicators,and so on.The results of NEP and other parameters were campared between the 3 groups.SPSS statistics 22.0 was used to peform the statistical analysis.The analytical methods mainly include the Kruskal-Wallis H test,the Chi-square test,the Spearman correlation coefficient analysis,and the ROC curve.Bilateral P value less than 0.05 was considered statistically significant.Results:1.The concentration of neprilysin was the highest in the control group(423.12pg/ml,IQR[248.94,905.04]pg/ml),which was significantly higher than that of the asymptomatic group(172.38pg/ml,IQR[87.26,242.44]pg/ml)and the symptomatic group(142.64pg/ml,IQR[61.84,305.53]pg/ml)(P(27)0.001).In contrast,the concentration of NT-proBNP was lowest in the control group: symptomatic group(1013.46pg/ml,IQR[540.39,2025.00]pg/ml)(29)asymptomatic group(617.00pg/ml,IQR[389.00,1126.00]pg/ml)(29)control group(100.00pg/ml,IQR [19.71,100.00]pg/ml)(all P(27)0.001).2.The concentration of neprilysin showed a certain correlation with NT-proBNP(r=-0.312,P(27)0.001).There was no correlation between neprilysin and LAD,e’,and E/e’(all P(29)0.05).3.ROC curve analysis showed that: in the control group and non-control group(asymptomatic group + symptomatic group),the curve area of NEP and NT-proBNP was 0.803(95% CI 0.743 to 0.863,P(27)0.001),0.991(95%)CI 0.981 to 1.001,P(27)0.001);in the control group and asymptomatic group,the curve area of NEP and NT-proBNP was 0.817(95% CI 0.747 to 0.887,P(27)0.001),0.984(95% CI 0.964 to 1.004,P(27)0.001);in the control group and symptomatic group,the curve area of NEP and NT-proBNP was 0.792(95% CI 0.724 to 0.859,P(27)0.001),and 0.997(95% CI 0.990 to 1.003,P(27)0.001).Conclusions:1.Plasma neprilysin levels were significantly reduced in patients of cardiac insufficiency with preserved ejection fraction,compared with those with normal cardiac function.2.Plasma neprilysin can be used as a biomarker for predicting cardiac insufficiency with preserved ejection fraction.